Comparative Safety of Bioabsorbable Polymer Everolimus-Eluting, Durable Polymer Everolimus-Eluting, and Durable Polymer Zotarolimus-Eluting Stents in Contemporary Clinical Practice.

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Outcomes with the polymer-based paclitaxel-eluting TAXUS stent in patients with diabetes mellitus: the TAXUS-IV trial.

OBJECTIVES: We sought to determine the safety and efficacy of polymer-regulated site-specific delivery of paclitaxel in patients with diabetes mellitus undergoing stent implantation. BACKGROUND: Percutaneous coronary intervention in patients with diabetes is associated with high rates of restenosis and repeat revascularization due to excessive neointimal proliferation, a process that may be blunted with the site-specific delivery of paclitaxel. METHODS: In the TAXUS-IV trial, 1,314 patients were prospectively randomized to the slow rate-release polymer-based paclitaxel-eluting TAXUS stent or the bare-metal EXPRESS stent (Boston Scientific Corp., Natick, Massachusetts). Medically treated diabetes was present in 318 patients (24%), 105 of whom required insulin. RESULTS: Among patients with diabetes, the TAXUS stent, compared to the bare-metal stent, reduced the rate of 9-month binary angiographic restenosis by 81% (6.4% vs. 34.5%, p < 0.0001), and reduced the 12-month rates of target lesion revascularization by 65% (7.4% vs. 20.9%, p = 0.0008), target vessel revascularization by 53% (11.3% vs. 24%, p < 0.004), and composite major adverse cardiac events by 44% (15.6% vs. 27.7%, p = 0.01). The one-year rates of cardiac death (1.9% vs. 2.5%), myocardial infarction (3.2% vs. 6.4%), and subacute thrombosis (0.6% vs. 1.2%) were comparable between the paclitaxel-eluting and control stents, respectively. In the insulin-requiring subgroup, the TAXUS stent reduced angiographic restenosis by 82% (7.7% vs. 42.9%, p = 0.0065), and reduced the one-year rate of target lesion revascularization by 68% (6.2% vs. 19.4%, p = 0.07), a relative reduction similar to patients without diabetes. CONCLUSIONS: The site-specific delivery of paclitaxel after coronary stent implantation is highly effective in reducing clinical and angiographic restenosis in patients with diabetes mellitus.

Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial.

CONTEXT: Compared with bare metal stents, drug-eluting stents reduce restenosis in noncomplex lesions. The utility of drug-eluting stents has not been evaluated in more difficult stenoses. OBJECTIVE: To investigate the safety and efficacy of the polymer-based, slow-release paclitaxel-eluting stent in a patient population with more complex lesions than previously studied. DESIGN, SETTING, AND PATIENTS: Prospective, placebo-controlled, double-blind, multicenter randomized trial conducted from February 2003 to March 2004 at 66 academic and community-based institutions with 1156 patients who underwent stent implantation in a single coronary artery stenosis (vessel diameter, 2.25-4.0 mm; lesion length, 10-46 mm), including 664 patients (57.4%) with complex or previously unstudied lesions (requiring 2.25-mm, 4.0-mm, and/or multiple stents) and 9-month clinical and angiographic follow-up. INTERVENTIONS: Patients were randomly assigned to receive 1 or more bare metal stents (n = 579) or identical-appearing paclitaxel-eluting stents (n = 577). MAIN OUTCOME MEASURE: Ischemia-driven target vessel revascularization at 9 months. RESULTS: Baseline characteristics were well matched. Diabetes was present in 31% of patients. The mean (SD) reference vessel diameter was 2.69 (0.57) mm, the reference lesion length was 17.2 (9.2) mm, and 78% of lesions were type B2/C. A mean (SD) of 1.38 (0.58) stents (total mean [SD] length, 28.4 [13.1] mm) were implanted per lesion; 33% of lesions required multiple stents. Stents that were 2.25 mm and 4.0 mm in diameter were used in 18% and 17% of lesions, respectively. Compared with bare metal stents, paclitaxel-eluting stents reduced the 9-month rate of target lesion revascularization from 15.7% to 8.6% (P<.001) and target vessel revascularization from 17.3% to 12.1% (P = .02). Similar rates were observed for cardiac death or myocardial infarction (5.5% for bare metal stent group vs 5.7% for paclitaxel-eluting stent group) and stent thrombosis (0.7% in both groups). Angiographic restenosis was reduced from 33.9% to 18.9% in the entire study cohort (P<.001), including among patients receiving 2.25-mm stents (49.4% vs 31.2%; P = .01), 4.0-mm stents (14.4% vs 3.5%; P = .02), and multiple stents (57.8% vs 27.2%; P<.001). CONCLUSION: Compared with a bare metal stent, implantation of the paclitaxel-eluting stent in a patient population with complex lesions effectively reduces clinical and angiographic restenosis.

A prospective evaluation of the safety and efficacy of the TAXUS Element paclitaxel-eluting coronary stent system for the treatment of de novo coronary artery lesions: design and statistical methods of the PERSEUS clinical program.

BACKGROUND: Paclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents. TAXUS Element is a third-generation paclitaxel-eluting stent which incorporates a novel, thinner-strut, platinum-enriched metal alloy platform. The stent is intended to have enhanced radiopacity and improved deliverability compared to other paclitaxel-eluting stents. The safety and efficacy of the TAXUS Element stent are being evaluated in the pivotal PERSEUS clinical trials. METHODS/DESIGN: The PERSEUS trials include two parallel studies of the TAXUS Element stent in single, de novo coronary atherosclerotic lesions. The PERSEUS Workhorse study is a prospective, randomized (3:1), single-blind, non-inferiority trial in subjects with lesion length < or = 28 mm and vessel diameter > or = 2.75 mm to < or = 4.0 mm which compares TAXUS Element to the TAXUS Express2 paclitaxel-eluting stent system. The Workhorse study employs a novel Bayesian statistical approach that uses prior information to limit the number of study subjects exposed to the investigational device and thus provide a safer and more efficient analysis of the TAXUS Element stent. PERSEUS Small Vessel is a prospective, single-arm, superiority trial in subjects with lesion length < or = 20 mm and vessel diameter > or = 2.25 mm to <2.75 mm that compares TAXUS Element with a matched historical bare metal Express stent control. DISCUSSION: The TAXUS PERSEUS clinical trial program uses a novel statistical approach to evaluate whether design and metal alloy iterations in the TAXUS Element stent platform provide comparable safety and improved procedural performance compared to the previous generation Express stent. PERSEUS trial enrollment is complete and primary endpoint data are expected in 2010. PERSEUS Workhorse and Small Vessel are registered at http://www.clinicaltrials.gov, identification numbers NCT00484315 and NCT00489541.

Clinical and angiographic outcomes after treatment of de novo coronary stenoses with a novel platinum chromium thin-strut stent: primary results of the PERSEUS (Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System) trial.

OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of the novel platinum chromium TAXUS Element paclitaxel-eluting stent (PES) compared with the TAXUS Express PES (Boston Scientific, Natick, Massachusetts) in treating coronary artery stenoses. BACKGROUND: The TAXUS Element is a novel thin-strut (81 microm), platinum chromium alloy PES designed to improve radial strength, radiopacity, and deliverability, while safely providing comparable restenosis benefit compared with a previous-generation PES. METHODS: The PERSEUS (Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System) Workhorse (WH) trial is a prospective, randomized (3:1), controlled, multicenter study of the TAXUS Element (vs. TAXUS Express) PES for the treatment of de novo coronary atherosclerotic lesionsor=2.75 to

Impact of mild or moderate renal insufficiency on the intravascular ultrasonic analysis of chronic vascular response to paclitaxel-eluting and bare-metal stents (from the TAXUS IV, V, and VI trials).

The presence of even mild renal insufficiency is usually associated with an increased rate of cardiovascular events after coronary stenting. The aim of this study was to evaluate the impact of mild to moderate renal insufficiency on the chronic vascular responses to the implantation of paclitaxel-eluting stents (PES; Taxus) and bare-metal stents (BMS). In the TAXUS IV, TAXUS V, and TAXUS VI trials, patients with serum creatinine levels >2.0 mg/dl were excluded. In the present analysis, 816 patients with serum creatinine levels or=80 ml/min/1.73 m(2)). For all levels of Ccr, patients with PES compared with those with BMS had less intimal hyperplasia area (group 1: 0.97 +/- 0.98 vs 2.94 +/- 1.89; group 2: 0.94 +/- 0.86 vs 2.30 +/- 1.21; group 3: 0.99 +/- 1.02 vs 2.53 +/- 1.29; group 4: 0.87 +/- 0.95 vs 2.12 +/- 1.29 mm(2), all p values <0.0001) and greater increases in peristent plaque and media area (group 1: 0.90 +/- 0.98 vs -0.02 +/- 0.98 mm(2), p = 0.03; group 2: 0.57 +/- 1.43 vs 0.20 +/- 1.14 mm(2), p = 0.11; group 3: 1.20 +/- 1.95 vs 0.02 +/- 1.17, p <0.0001; group 4: 0.35 +/- 1.44 vs -0.19 +/- 1.08 mm(2), p = 0.08). Neointimal growth and vessel remodeling were not affected by variations in Ccr after either BMS or PES implantation over the range studied. The incidence of incomplete stent apposition at follow-up was lowest in patients with the greatest renal impairment after BMS and PES implantation. In conclusion, neointimal proliferation was less prominent and expansive vessel remodeling was more prominent after PES than BMS implantation, independent of the severity of renal dysfunction.

Effect of the polymer-based, paclitaxel-eluting TAXUS Express stent on vascular tissue responses: a volumetric intravascular ultrasound integrated analysis from the TAXUS IV, V, and VI trials.

AIMS: The TAXUS Express stent has been shown to reduce angiographic restenosis, repeat revascularizations, and neointimal hyperplasia when compared with bare metal stent (BMS) control (TAXUS IV, V, and VI) in individual TAXUS trials. Since intravascular ultrasound (IVUS) methodology and core laboratory were consistent among all three TAXUS trials, an integrated analysis of 956 patients across all IVUS cohorts can be performed providing superior power. METHODS AND RESULTS: In the TAXUS randomized trials, patients received an Express BMS or paclitaxel-eluting TAXUS Express stent. Volumetric analysis was performed on a selected subgroup at implantation and 9 months. Compared with BMS control, TAXUS increased 9-month lumen volumes (144 +/- 79 vs. 179 +/- 95 mm(3); P < 0.0001) due to reduced neointimal volume (66 +/- 49 vs. 27 +/- 30 mm(3); P < 0.0001). This corresponded to a 61% decrease in net lumen volume obstruction (31 +/- 15 vs. 12 +/- 12 mm(3); P < 0.0001). Lumen loss was similar between groups for the proximal 5 mm outside the stent but was reduced in TAXUS at the distal edge (P = 0.0056). Neointimal hyperplasia was significantly reduced in the double-strut region of overlapping TAXUS vs. BMS control and in high-risk patients with diabetes, long lesions, multiple stents, and multiple overlapping stents. Late-acquired incomplete stent apposition (ISA) was more common with moderate-release TAXUS stents. Importantly, there were no major adverse cardiac events or stent thromboses in any late-acquired ISA patient through 2 years. Univariate and multivariable analyses revealed that longer lesion length and previous myocardial infarction are risk factors for late-acquired ISA. CONCLUSION: Integrated analysis of the TAXUS trials shows that the paclitaxel-eluting TAXUS Express stent effectively inhibits in-stent neointimal proliferation, even in high-risk and overlapping stent patients.

Polymer-based, paclitaxel-eluting TAXUS Liberté stent in de novo lesions: the pivotal TAXUS ATLAS trial.

OBJECTIVES: The goal of this research was to assess non-inferiority of the next-generation TAXUS Liberté stent (Boston Scientific Corp., Natick, Massachusetts) versus the TAXUS Express stent (Boston Scientific Corp.). BACKGROUND: The introduction of drug-eluting stents (DES) has shifted clinical practice towards more complex lesion subsets, prompting the need for more deliverable DES. TAXUS Liberté was designed to combine the established polymer-based, paclitaxel-elution TAXUS technology with the more advanced Liberté stent platform. METHODS: The TAXUS ATLAS study is a global, prospective, single-arm trial evaluating outcomes in de novo coronary lesions visually estimated to be 10 to 28 mm in length in vessels 2.5 to 4.0 mm in diameter. The control group is an entry-criteria-matched population of TAXUS Express patients from the TAXUS IV and V trials. The primary end point is non-inferiority of TAXUS Liberté versus TAXUS Express for 9-month target vessel revascularization. RESULTS: Despite similar inclusion criteria, quantitative coronary angiography-determined baseline lesion characteristics were significantly more complex for TAXUS Liberté than TAXUS Express. The primary non-inferiority end point was met with the 1-sided 95% confidence bound of 2.98% less than the pre-specified non-inferiority margin of 3% (p = 0.0487). CONCLUSIONS: Despite the treatment of more complex lesions with TAXUS Liberté, the primary end point was met, demonstrating that TAXUS Liberté is non-inferior to TAXUS Express. The successful transfer of the proven TAXUS technology to the more advanced TAXUS Liberté platform was demonstrated. (TAXUS ATLAS: TAXUS Liberté-SR Stent for the Treatment of De Novo Coronary Artery Lesions; http://www.clinicaltrials.gov/ct/show/NCT00371709?order=1; NCT00371709).

Clinical experience with a circumferential clip-based vascular closure device in diagnostic catheterization.

BACKGROUND: The StarClose Vascular Closure System (Abbott Vascular Devices, Redwood City, California) utilizes a small, flexible nitinol clip to complete a circumferential, extravascular closure of the femoral arteriotomy site. The StarClose is an investigational device in the United States, limited by Federal law to investigational use. The StarClose is CE Mark approved. METHODS: The CLIP study was a prospective, randomized, multicenter trial utilizing a noninferiority design to compare the rate of major vascular complications and time-to-hemostasis using the StarClose system versus manual compression. A total of 596 subjects were enrolled, 208 of whom underwent diagnostic angiography. This diagnostic subset is the focus of this report. The primary safety endpoint was major vascular complications and the primary efficacy endpoint was time-to-hemostasis. All patients were followed at 30 days with a clinical exam. RESULTS: Subjects were randomized 2:1 to the StarClose (n = 136) or manual compression (n = 72). There were no major vascular complications in either group. Minor vascular complications occurred in 3 StarClose patients (2.2%), and 1 manual compression patient (1.4%) (p = 1.00). Use of the StarClose device reduced mean time-to-hemostasis from 15.47 +/- 11.4 to 1.46 +/- 4.5 minutes (p < 0.001) when compared to manual compression, and reduced the average time-to-ambulation from 269 +/- 135 to 163 +/- 105 minutes (p < or = 0.001). Device success was 94.1% (127/135), and procedural success was 100% (136/136). CONCLUSION: The clinical results of this study concluded that the StarClose Vascular Closure System is noninferior to standard compression with respect to the the primary safety endpoint of closing arteriotomies in patients who undergo percutaneous diagnostic procedures.